Cha J Y, Birsoy B, Kofron M, Mahoney E, Lang S, Wylie C, Heasman J
Department of Biomedical Engineering, University of Cincinnati, Cincinnati, Ohio, USA.
Dev Dyn. 2007 Oct;236(10):2731-41. doi: 10.1002/dvdy.21240.
FoxC1 is an important transcription factor in vertebrate development since its mutation in humans results in Axenfeld-Rieger syndrome. In the mouse, disturbance of its function causes congenital hydrocephalus and abnormalities in the development of various mesodermal derivatives. In this report, we provide one mechanistic basis for the requirement for FoxC1 in vertebrate development. We find that, in Xenopus laevis embryos, FoxC1 expression is regulated by the maternal T-box transcription factor VegT, via the nodal sub-family of TGFbeta signaling transducers. We show that at the late neurula to early tailbud stage, FoxC1 depletion causes the down-regulation of adhesion molecules, EP and E cadherin, as well as members of the Ephrin/EphR signaling families in the mesoderm germ layer resulting in the loss of adhesion and apoptosis of mesodermal cells.
FoxC1是脊椎动物发育过程中的一种重要转录因子，因为其在人类中的突变会导致Axenfeld-Rieger综合征。在小鼠中，其功能紊乱会导致先天性脑积水以及各种中胚层衍生物发育异常。在本报告中，我们为脊椎动物发育过程中对FoxC1的需求提供了一种机制基础。我们发现，在非洲爪蟾胚胎中，FoxC1的表达受母体T-box转录因子VegT通过TGFβ信号转导子的节点亚家族调控。我们表明，在神经胚晚期至早期尾芽阶段，FoxC1缺失会导致中胚层胚层中黏附分子EP和E-钙黏蛋白以及Ephrin/EphR信号家族成员的下调，从而导致中胚层细胞黏附丧失和凋亡。
